2. LEUKEMIA
• Leukemia are the neoplastic proliferation of
hemopoietic cells.
• Acute leukemias are defined as neoplsam
• AML - more than 20 % blast
• ALL- more than 25% blast.
3. • Commonest form of malignancy in childhood.
• Peak incidence at 4 – 5 yrs of age.
• Acute onset with short history of duration.
• 85% are B cell , 15% are T cell.
ACUTE LYMPHOBLASTIC
LEUKEMIA
5. • Activation of a proto-oncogene to an oncogene when it
is translocated to a transcriptionally active site
• Formation of a chimeric transcription factor
• Formation of a fusion protein with enhanced tyrosine
kinase activity
• Activation of FTL3 receptor
• Inactivation of tumour suppressor gene pathway
MECHANISM OF LEUKAEMOGENESIS
6. SYMPTOMS
• FEVER
• FATIGUE
• BONE /JOINTS PAIN
• WEIGHT LOSS
• PURPURA AND BLEEDING MANIFESTATION
• LYMPHADENOPATHY
• HEPATOSPLENOMEGALY
• STERNAL TENDERNESS
• MEDIASTENAL MASS
7. FAB CLASSIFICATION
• Based on morphology and cytochemistry.
•
stain AML ALL
MPO + -
SBB + -
NSE + IN M4, M5 AND M7 -
PAS FINE + IN M6 , M7 + , BLOCK
ACID PHOSPHATASE - +, T ALL
8. FAB CLASSIFICATION
ALL L1
ALL L2
ALL L3
In childhood – L1 is the most common type
In adults – L2 is the most common type
9. FAB classification
Morphology L1 L2 L3
1 Size of blast Small Large
heterogeneous
Large
homogenous
2 Cytoplasm Scanty Moderate Moderate,
intensely
basophilic
3 N/C Ratio High Lower Lower
4 Cytoplasmic vacuoles +/- +/- Prominent
5 Nuclear membrane Regular Irregular with clef
ting
Regular
6 Nucleoli Invisible /
indistinct
Prominent 1-2 Prominent 1-2
10. CRITICISM OF FAB CLASSIFICATION
1- It dose not include
• Immunophenotyping
• Cytogentics
• Molecular characteristics
2- immunological subtype of ALL
3-biphenotypic leukemia
4- Limited relevance to therapeutic or
prognostic implications.
11. WHO CLASSIFIACTION OF ALL (2008)
1-B lymphoblastic leukemia/lymphoma nos
2- B lymphoblastic leukemia/lymphoma with recurrent
abnormalities
• t( 9; 22) , BCR ABL1
• t( v; 11q23) MLL rearangement
• t (12;21) ETV6-RUNX1
• With hypodiploidy
• With hyperdiploidy
• t (5;14) il3 –igh
• t ( 1;19) E2A-PBX1 (tcf3-pbx1)
3-T lymphoblastic leukemia/lymphoma
12. IMMUNOLOGICAL CLLASIFICATION
• 1- B ALL
• PRO B ALL
• EARLY PRE B ALL
• PRE B ALL
• MATURE B ALL
• 2- T ALL
• 3- MIXED LINEAGE ACUTE LEUKEMIA
• 4-Undifferentiated acute leukemia
14. T ALL
• PAS negative acid phosphatase positive
• CNS involvement and mediastenal mass
• CD3 ,2 and 7 positive
15. Scoring system for biphenotypic leukemia
points B lineage T lineage Myeloid
2.0 CD 79a
CD 22.
CD 3 MPO
1.0 CD 10 CD 1 CD 13
0.5 TdT TdT, CD 7 CD 11b
CD 11c
Score above 2 from two lineage is diagnostic of biphenotypic leukemia
16. Uncommon variants of ALL
• Small cell variant- blast cells are small and
may be mistaken for lymphocytes.
• Hand mirror variants- a subtype with
cytoplasmic protrusion .
• ALL with eosinophilia
• Granular cell ALL- The cells are large and
demonstrate azurophilic granulaes .
19. PERIPHERAL BLOOD EXAMINATION
• Total leucocyte count raised , normal or low.
• Normocytic normochromic anaemia.
• Thrombocytopenia.
20.
21. • Subleukemic leukemia-Total leukocyte count
is normal or low , but blast are seen in the
peripheral blood.
• Aleukemic leukemia- Blast are not seen in the
peripheral blood , but are demonstrable only
in bone marrow.
35. DIFFERENTIAL DIAGNOSIS
• Leukemic phase of Non Hodgkins Lymphoma
• Reactive lymphocytosis due to infections
• Metastatic tumours in bone marrow
• AML
36. ALL Vs AML
ALL AML
Age Mainly children Mainly adults
Lymphadenopathy Usually present Usually absent
Hepatosplenomegaly +ve mild +ve mild
Gum hypertrophy -ve +ve in M4/M5
Skin infiltration -ve +ve in M4/M5
CNS involvement +ve in some +ve in some
Granulocytic sarcoma -ve +ve in few cases
Mediastinal mass +ve in T-ALL -
Associated DIC -ve +ve in M3
Serum muramidase Normal In M4/M5 (monocytic type)
Prognosis Good Bad
37. MorphologyLymphoblast Myeloblast
Nuclear chromatin Coarse Fine
Nucleoli 1-2 3-5
N:C ratio High High
Auer rod -ve +ve
Accompanying
cells
Lymphocytes Myeloid precursor
Myelo peroxidase -ve +ve
Sudan Black B -ve +ve
PAS stain Block positivity -ve in blast
39. PROGNOSTIC FACTORS
Factor Good prognosis Bad prognosis
Race White Black
Age 2-8 yrs <1yr.,adult, >10 yrs
Sex Female Male
Meningeal involvement - +
Lymphadenopathy, liver,
spleen
- Massively enlarged
Mediastinal mass - +
TLC <20x109
/L >50 x109
/L
Type of ALL L1 L2,L3
Cytogenetics Hyperdiploidy >50
chromosomes
Pseudodiploidy, t (4;11),t (9;22), BCR-ABL
fusion m RNA, MLL-AF4 fusion mRNA.
Immuno-phenotype B-ALL,CD 10+, Early pre-B
cell
T-ALL in children
40. Minimal residual disease detection
– ALL – B cell
– Cd20/cd10/cd19/cd45
– Cd9/cd34/cd19/cd45
– Cd58/cd10/cd38/cd19
– Cd20/cd10/cd19/cd34
– ALL –T cell
– TdT/CD5/CD3/CD7
41.
42. • MODERATOR— Prof. Dr. C. V. KULKARNI
• SPEAKER- DR. NARMADA PRASAD TIWARI